Topic: San Antonio Breast Cancer Symposium Updates Posted: Dec 16 2014 at 10:27am
San Antonio Breast Cancer Symposium 2014
A Report to the Triple Negative Breast Cancer Community
Post 4 | December 16, 2014
Wrap Up: The Doctor’s Perspective
Linda Vadhat, MD, is a breast cancer specialist and researcher from
Weill Cornell Medical Center in New York City. She provided insight into
the 2014 San Antonio Breast Cancer Symposium.
In her view, this year’s meeting had a number of very positive
take-aways for the triple negative breast cancer community, but no one
major practice changing development.
“I have to say there is a real emphasis right now on triple negative
breast cancer and on understanding the biology--the genomics, the
immunology, the stem cells. These are all very important steps forward,
although they are just beginning to have an impact on the clinical
outcomes for triple negative patients.”
Dr. Vadhat said that she thought the Phase I trial of pembrolizumab
(Keytruda) was an excellent example of an important first step. She
noted that the five responders (out of 27 in the trial) were not the
patients who had high levels of PD-1 expression. “We are very encouraged
by the activity of this group of drugs, but we really aren’t sure right
now whether PD-1 is a biomarker. We need to know more about how these
drugs work and in which patients they work.”
She also pointed to the trial that compared paclitaxel (Taxane) with
nab-placlitaxel (Abraxane) as useful but not landscape changing. “The
dose of Abraxane was a little higher than that of paclitaxel, so we have
to wonder a little about that. Abraxane is also a very expensive drug
and cost is becoming more of a factor for some patients in making
decisions. It’s important to have these data and this option for our
patients in the neoadjuvant setting where we can really make a
difference.”
Vadhat believes that understanding the subtypes of triple negative
breast cancer will become increasingly significant in developing
effective treatment. “We need to know what’s driving these cancers to
treat them effectively, and it is now clear that there are distinct
biological characteristics that influence how these cancers grow and
spread--and that we will be able to target in the future.”
In her own research, Vadhat focuses on inhibiting copper dependent
processes as a way of preventing invasion and metastases in triple
negative breast cancer patients. Copper is essential to the ability of
cancer cells to form blood vessels, especially in the microenvironment
around the tumor. Vadhat has concluded a Phase I study and is planning a
larger Phase II study in this promising area.
She also believes that in the near future, we will move from talking
about cancers in terms of the organ or site in which they develop to
describing them by their genomic characteristics.
A Conversation with Kathy Swiger about the LBBC Survey of Triple Negative Breast Cancer Patients
Kathy Swiger stands by her poster in the “Psychosocial and Behavioral”
Section of the vast hall at the San Antonio Breast Cancer Symposium. the
second of two that Living Beyond Breast Cancer (LBBC) has presented at
this important meeting. There’s a lot interest from the attendees, both
advocates and clinicians. They study the data and ask Swiger questions
about the results.
“The posters are just the tip of the iceberg,” she says pointing the
densely worded panels behind her. “There is so much more data in the
full survey.”
Swiger is the lead investigator on the study and clearly has a deep
passion for her work. She notes that before the actual survey, the LBBC
team conducted a series of focus groups across the country to identify
issues important to the TNBC community.
“In some areas, we had women who drove four hours to participate in a
focus group. It was that important to them to have their voices heard
and to have the chance to talk to people who were sharing their
experience. In San Francisco, the group asked if we would pay for
another two hours of parking so they could go to lunch together after
the session--and keep talking to each other. We found that many of these
women feel very isolated. Their experience is different from that of
other people with breast cancer.”
For some women, this isolation is geographic--being in an area in which
there are few others with a tnbc diagnosis. That could be either rural
or urban. For others, it stems from an age discrepancy--or huge
differences in the treatment course. One young African American woman
from a small town in North Carolina talked about going to a support
group in which all the other participant were older women dealing with
the effects of hormone therapy.
Swiger also noted that many of the focus group participants struggle
with the term “triple negative.” “We found that many people have never
heard of triple negative breast cancer, or know little about it before
their diagnosis. They hear the term triple negative and to some it
sounds like ‘three strikes and you’re out.” It’s very frightening. Then
they look online and what they find can be scary and confusing.”
The focus groups were to used to develop the survey which compared the
responses of 656 triple negative patients with those of 1954 women with
other breast cancer subtypes. The survey revealed significant
differences in the kinds of information the tnbc patients want and the
levels of anxiety, fear and worry they experience from diagnosis to
treatment. The full survey results will be made public in early 2015.
“There is such a strong need among the triple negative patients both
for information that is specific to their disease and what they are
experiencing,” says Swiger, “and for person to person peer interaction,
the opportunity to share those experiences. This survey is just a first
step in addressing the information and emotional support needs of this
group of people.”
The Triple Negative Breast Cancer Foundation worked with LBCC to
identify potential responders for the survey. TNBCF also sponsored the
first triple negative specific track at LBCC’s annual conference held in
September in Philadelphia. That support included scholarships to bring
people with TNBC to the conference from all over the country. TNBCF has
committed to repeating that sponsorship in 2015.
A Report to the Triple Negative Breast Cancer Community
Post 3 | December 12, 2014
Take Aways...
Here are some “take-aways” from this year’s San Antonio
Breast Cancer Conference. Let’s start with two issues that have been the center
of discussion and study over the last few years.
Is pathological
complete response (pCR) an acceptable endpoint for evaluating the success of a
clinical trial? The standard clinical trial is structured to measure one or
more of these criteria:
●Overall response rate (ORR)--the percentage of
participants in the study who get a complete or partial response to the therapy
being tested
●Disease free survival (DFS)--the length of time that a
person remains without detectable disease from the time of treatment
●Progression free survival (PFS)--the length of time from
treatment until the cancer begins to grow again. This is sometime called
relapse free survival (RFS).
The advent of neo-adjuvant therapy has led to a new
criterion--whether the treatment causes all visible signs of the cancer to
disappear before the primary treatment, usually surgery. In medical terms this
is called a pCR. Initially, there were questions as to whether a pCR correlates
with improved survival or better outcomes, but that debate has ended. The
evidence is now solid that patients who achieve a pCR have lower rates of
recurrence and longer survival than those who do not. This has been clearly
demonstrated in people with TNBC.
The advantages of neoadjuvant therapy are clear for the TNBC
population. Women who are treated successfully with their initial therapy do
well, those who recur face a difficult and often limited clinical course. The
goal of treatment is to prevent recurrence in as many people as possible.
Neoadjuvant therapy improves those odds. Using pCR as an outcomes measures also
allows for faster assessment of whether drugs are effective and more flexible
clinical trials.
At SABCS 14, a neoadjuvant trial comparing single agent
paclitaxel (Taxane) and nab-paclitaxel (Abraxane) in 400 women with high risk,
early breast cancer showed a clear advantage for the Abraxane arm.Thirty-eight percent of the women in the
Abraxane arm achieved a pCR vs. 29% of the Taxane arm. Both groups received
standard chemotherapy as part of the regimen.
considered standard of care for TNBC patients with BRCA1
mutations.
Should platinum based
chemotherapy be standard therapy for some subsets of TNBC patients? The
data are now convincing on this issue as well. Platinum based chemotherapy is
now considered standard of care for TNBC patients with germline BRCA1 and 2
mutations. This is true for both early stage and metastatic disease.
New Trial to Test
Immunotherapy/Chemo Combination On another front, a Phase I trial on which Celgene and
Bristol Myers Squibb are collaborating opened today (12/12). The study will
take place at 15 centers across the United States and involve three cohorts of
patients, one with pancreatic cancer, one with non small cell lung cancer, and
one with TNBC and HER2- breast cancers. These patients will receive three
cycles of nab-paclitaxel (Abraxane) and be randomized to receive or not receive
nivolumab (Opdivo),a PD-1 checkpoint
inhibitor that has shown activity in a number of cancer types. The patients in
the trial will all have recurrent or metastatic disease and have failed one previous
treatment. This is a Phase I trial designed to establish safety and preliminary
effectiveness, but it is also one of the first trials to combine chemotherapy
with immunotherapy for breast cancer patients.
Weight Management
Makes a Difference for TNBC Patients The WINS trial may sound like ancient history. It was opened
in 1994 to study if reducing dietary fat for women with early stage breast
cancer improves survival. The trial enrolled patients who consumed at least 20%
of their calories in fat and randomized them into those who got an
intervention--reduced fat--and those who did not. The follow was shaky but, in
the final analysis, presented at SABCS 14, there was no significant difference
in overall survival between the two groups--except in the subgroup of women
with hormone receptor negative disease. Researchers believe that the real
benefit came from weight loss and increased physical activity as opposed to fat
reduction. The NCI is reviewing for a large scale study on lifestyle factors
and cancer survival and two trials are currently underway in Europe looking at
dietary factors and physical activity.
As the meeting wraps up, what are the important messages for
the TNBC community?
●Immunotherapy is rapidly emerging as a very promising
area of treatment for triple negative breast cancer.
●This work is still in its early phases. A great deal
more research needs to be done to determine how best to use these new agents,
which patients will benefit, how to combine them with other therapies and in
what circumstances and sequences to use them.
●Although the goal of defining a targeted therapy for
TNBC that is the equivalent of Herceptin remains elusive, treatment for this
disease is becomingly increasingly individualized. A key to this is identifying
the subtypes of TNBC and understanding the clinical significance of these
biological differences in making treatment decisions.
●Neoadjuvant therapy is improving the odds for newly
diagnosed TNBC patients, lowering the risk of recurrence.
The next report will include comments from two experts on
the importance of this meeting and an expanded interview with the investigator
who conducted the LBCC survey of people with TNBC.
San Antonio Breast Cancer Symposium 2014
A Report to the Triple Negative Breast Cancer Community
Post 2 | December 11, 2014
A Promising Study--An Important Step Forward
"Let's not wait. Let's move these trials forward so we can benefit our triple negative breast cancer patients."
- Nora Disis, MD
A Phase I study of a new immunotherapy agent has produced promising
results in a subset of patients with advanced triple negative breast
cancer. The drug, prembrolizumab (Keytruda), is one of a group of very
promising agents that block the PD-1 protein on the surface of cancer
cells. The study, presented on December 10, at the San Antonio Breast
Cancer Symposium is an example of the rapid progress being made in the
area of immunotherapy, but also comes with some with precautions about
what this study means and where it will lead.
Prembrolizumab got a lot of attention at the 2014 meeting or the
American Society of Clinical Oncology when the results of a trial using
this new monoclonal antibody to treat advanced melanoma were announced.
Prembrolizumab, also known as MK-3475, produced such positive responses
in this population that the drug was given accelerated approval by the
Food and Drug Administration and approved for this use in October.
Studies for other tumor types including lung, bladder and head and neck
cancers have had response rates of between 20-34%. These results were
important because they occurred in patients with advanced disease and
many of the responses were long lasting.
The KEYNOTE-012 study results were reported by Rita Nanda, MD, of the
University of Chicago. This was a very small, Phase I trial in which 32
women with advanced triple negative breast cancer were given
prembrolizumab as a single agent. All of these patients had received
multiple chemotherapy regimens prior to entering the study. The overall
response rate was 18.5% or five patients. One woman had a complete
response, four had partial responses. An additional seven had stable
disease. What is significant is that the five responders remain in
remission more than 11 months after starting treatment--an extraordinary
durable response for this group of patients. Two are still on treatment
and two discontinued the therapy after 40 weeks.
The side effects seen in this trial were generally mild and tolerated
well. They included rashes, fatigue and joint pain. One patient had
hypothyroidism. Overall 56% of the treated patients had some reported
side effects, mostly grade I and 2.
Prembrolizumab works as what is known as a checkpoint blocker. Cancer
cells can block T cells from attacking them by expressing PD-1 and its
ligands PD-L1 and PD-L2 on their surface. Prembrolizumab and other
checkpoint blockers inhibit that expression and allow T cells to
recognize and destroy the cancer cells. The study included only patients
whose tumors were identified as expressing PD-1--approximately 60% of
triple negative patients.
An interesting side note to this report was the difference in how two
audiences reacted to the study results. I heard these data presented
twice, first to a group of medical and scientific reporters at the press
conference, and then to the packed auditorium of cancer specialists
attending the symposium. The reporters were skeptical, asking "given the
relatively low response rate, is this really a positive study?" The
medical people were excited and encouraged by the study results, seeing
this as a potentially important step forward in developing new
treatments for TNBC and a solid basis for continuing studies.
"These results are right in the ballpark with what we are seeing with
other tumor types, said Dr. Disis who led the discussion of the session.
"We have the biology, the response rates and the toxicity we are seeing
across the board. It's time to move onward. We are looking for a better
therapy that will cause long lasting protective immunity."
Both the presenters and the discussant stressed the importance of
conducting additional trials with larger groups of patients, identifying
the factors in addition to being PD-1 positive that predict response
and combining pembrolizumanb with other agents to increase the overall
response rate. A larger, multicenter Phase II trial is planned for early
2015.
San Antonio Breast Cancer Symposium 2014
A Report to the Triple Negative Breast Cancer Community
Post 1 | December 10, 2014
“The work done in the last three or four years has put breast cancer at the forefront of immunotherapy.” - Nora Disis, MD, University of Washington
Greetings from San Antonio.
There’s a buzz this year.
Oncologists don’t get excited too easily. They are a cautious group,
driven by data, veterans of a world in which many studies fail, progress
is often measured in inches and new discoveries reveal deeper
complexities. This year, it’s different. There’s a growing belief that
we are on the verge of new era in cancer treatment that has the
potential to change the way we think about cancer and the way people
experience these diseases.
The reason for this excitement is the emergence of immunotherapy to
treat a wide range of cancers--including breast cancer. Immunotherapy
harnesses the body’s natural defenses to recognize and fight cancers.
The principle sounds simple enough, but the reality of immunotherapy is
amazingly complex, requiring an ever deeper understanding of the ways in
which cancers interact with the immune system.
For people facing triple negative breast cancer, immunotherapy could
open the doors to new therapies and new hope both for curing early TNBC
and for greatly improving the outcomes for advanced disease. While it is
important to realize that all of this work is in its early stages, the
rapidity with which new knowledge is being translated into new
treatments means that patients will have access to these new approaches
beginning now and the options will increase within the next few years.
It is also important to know there are currently no immunotherapy drugs
approved to treat breast cancer. All breast cancer related immunotherapy
research is being done in cancer centers through clinical trials.
TNBC: “The Hallmark of Immunogenic Cancers”
Researchers have known for decades that some cancers are
immunogenic--meaning that the immune system appears to recognize these
cells as abnormal or foreign, and at least, in some cases, react to
them. Melanoma and kidney cancers topped that list. As immunotherapy has
progressed, other cancers, including lung, bladder and hematologic
cancers have also been shown to respond to these approaches. Breast
cancer was not thought to be a good candidate for immunotherapy. New
work, however, demonstrates a strong connection between the immune
system and some breast cancers. Triple negative is in the words of Dr.
Disis, “the hallmark of immunogenic breast cancers.”
Tumor Infiltrating Lymphocytes
One study presented today looked at the correlation between tumor
infiltrating lymphocytes (TILs) in the stroma or tissue environment
around the tumor and responses to chemotherapy. TILs are indicators that
the immune system is responding to the tumor. Previous studies have
reported that patients with stromal TILs have a better prognosis and
respond better to chemotherapy than those who do not. The trial, led by
Edith Perez, MD, of the Mayo Clinic, Jacksonville, Florida found that
patients with large numbers of lymphocytes (lymphocyte predominant
breast cancer or LPBC) have increased recurrence free survival compared
to those with non-LPBC tumors. Approximately, 60% of TNBC is lymphocyte
predominant.
Why is this important? First, it provides an important marker for
identifying which TNBC patients are most likely to respond well to
adjuvant and neoadjuvant therapies and to treatment for advanced
disease. Second, it creates the possibility of developing new treatments
aimed at getting more lymphocytes into tumors in order to enhance the
immune response. Third, there are certain genetic mutations that are
associated with immune suppression--the BRAF mutation, for example,
found in about 50% of melanoma patients. BRAF inhibitors are known to
increase two key indicators of immune response---knowledge that could be
applicable to TNBC in the future.
In the next few days, we will report on other key findings from this
remarkable symposium, including a Phase I study on an immunotherapy
agent in triple negative breast cancer patients.
Living Beyond Breast Cancer Survey Reports High Levels of Anxiety for People with All Stages of TNBC
The first survey of psychosocial needs for women with triple negative
breast cancer reports that women with this disease have higher levels of
fear, anxiety and worry at all stages than women with other breast
cancer subtypes. The study also showed that TNBC patients have a
significantly stronger preference for information tailored to their
cancer subtype. Living Beyond Breast Cancer (LBCC) partnered with the
Triple Negative Breast Cancer Foundation to identify patients and
conduct the survey.
“Women with triple negative breast cancer are information seekers.”
Jean Sachs, MSS, MLSP CEO of LBCC said. “And they are frustrated when
they don’t have more treatment options.”
One striking finding was the extent to which TNBC patients continue to
feel fear and anxiety at all points of their diagnosis and treatment.
“While women with all breast cancer subtypes report a reduction in
negative emotion over time from treatment to post treatment, this change
is less profound in TNBC women and appears to be driven nearly entirely
by concern about the disease,” the study found.
The study was conducted between November 2013 and January 2014 and
compared responses of 656 women diagnosed with TNBC with those of 1954
women with other subtypes of breast cancer. The results of the survey
are being presented at two SABCS poster sessions. LBCC will release a
public summary of the finding in January 2015.
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